17-34038981-A-G

Variant names:

• chr17-34038981-A-G
• rs3744516
• ENST00000359872.6:c.555+116997T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001094.5(ASIC2):​c.555+116997T>C variant causes a intron change. The variant allele was found at a frequency of 0.556 in 1,613,800 control chromosomes in the GnomAD database, including 259,229 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (34967 hom., cov: 33)
  • Exomes 𝑓: 0.55 (224262 hom.)
• Consequence: ASIC2 NM_001094.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17
• Publications: 7 publications found

Genes affected

ASIC2 (HGNC:99): (acid sensing ion channel subunit 2) This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene may play a role in neurotransmission. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 3 has been observed to co-assemble into proton-gated channels sensitive to gadolinium. Alternative splicing has been observed at this locus and two variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Feb 2012]

TLK2P1 (HGNC:18048): (tousled like kinase 2 pseudogene 1)

ENSG00000265356 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001094.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	NM_001094.5		c.555+116997T>C		intron	N/A	NP_001085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC2	ENST00000359872.6	TSL:1	c.555+116997T>C		intron	N/A	ENSP00000352934.6	Q16515-1
	TLK2P1	ENST00000530992.1	TSL:6	n.892T>C		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000265356	ENST00000636421.1	TSL:5	n.458+2253T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99613 AN: 152012 Hom.: 34906 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.546 AC: 797519 AN: 1461670 Hom.: 224262 Cov.: 51 AF XY: 0.547 AC XY: 398038 AN XY: 727142

African (AFR) AF: 0.925 AC: 30975 AN: 33478

American (AMR) AF: 0.735 AC: 32881 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 13927 AN: 26136

East Asian (EAS) AF: 0.780 AC: 30951 AN: 39698

South Asian (SAS) AF: 0.660 AC: 56888 AN: 86250

European-Finnish (FIN) AF: 0.558 AC: 29811 AN: 53418

Middle Eastern (MID) AF: 0.601 AC: 3468 AN: 5766

European-Non Finnish (NFE) AF: 0.508 AC: 564455 AN: 1111810

Other (OTH) AF: 0.566 AC: 34163 AN: 60396

GnomAD4 genome AF: 0.656 AC: 99736 AN: 152130 Hom.: 34967 Cov.: 33 AF XY: 0.657 AC XY: 48873 AN XY: 74386

African (AFR) AF: 0.909 AC: 37746 AN: 41514

American (AMR) AF: 0.649 AC: 9908 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1897 AN: 3472

East Asian (EAS) AF: 0.751 AC: 3888 AN: 5180

South Asian (SAS) AF: 0.666 AC: 3210 AN: 4820

European-Finnish (FIN) AF: 0.552 AC: 5837 AN: 10574

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35091 AN: 67976

Other (OTH) AF: 0.619 AC: 1309 AN: 2114

Alfa AF: 0.565 Hom.: 40526

Bravo AF: 0.676

Asia WGS AF: 0.706 AC: 2453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.0
DANN	Benign	0.65
PhyloP100		5.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3744516; hg19: chr17-32366000;